The bone marrow is an important dose limiting cell renewal tissue for both chemotherapy and wide field irradiation. The purpose of this project is to study the stem cell compartment of the bone marrow; specifically its organization and what implications its organization has in the clinical use of chemotherapeutic agents and irradiation. We shall test our theory of stem cell organization as it relates to late effects of chemotherapy and to bone marrow transplantation. We shall study the use of in vitro techniques to best prepare bone marrow for transplantation while avoiding graft versus host disease. We shall determine whether we can use the in vitro technique to develop functional marrow made resistant to chemotherapeutic agents. We shall study the best mechanism of preparing the host for bone marrow transplantation to reduce the toxicity of such treatment yet not limit its efficacy. These projects have obvious clinical implications in cancer chemotherapy, radiation therapy and bone marrow transplantation.